Biallelic Variant in SLC6A17 in a Pakistani Family With Autosomal Recessive Intellectual Disability

Area of Science:

• Genetics
• Neurodevelopmental Disorders
• Human Molecular Genetics

Background:

• Autosomal recessive intellectual disability is a significant genetic disorder with a prevalence of 1%-33%.
• Mental Retardation Autosomal Recessive 48 (MRT 48) is a rare syndromic form characterized by progressive tremors, speech issues, and behavioral problems.
• Consanguineous marriages increase the incidence of autosomal recessive disorders in certain populations.

Purpose of the Study:

• To investigate the genetic basis of Mental Retardation Autosomal Recessive 48 (MRT 48) in a consanguineous family.
• To identify novel variants associated with intellectual disability.
• To expand the known genotypic spectrum of SLC6A17-related disorders.

Main Methods:

• Whole exome sequencing was performed on the index patient.
• Segregation analysis was conducted in the extended family to confirm the variant's inheritance pattern.
• Clinical phenotyping was performed to correlate genotype with observed symptoms.

Main Results:

• A homozygous c.1693T>C;p.(Tyr565His) variant in the SLC6A17 gene was identified in the affected individual.
• This SLC6A17 variant segregated with the intellectual disability phenotype within the family.
• The findings implicate SLC6A17 as a causative gene for MRT 48.

Conclusions:

• The study identifies a novel pathogenic variant in SLC6A17 associated with Mental Retardation Autosomal Recessive 48.
• This expands the genotypic spectrum of SLC6A17 variants and contributes to understanding the genetic causes of intellectual disability.
• Genetic diagnosis is crucial for families with intellectual disability, especially in consanguineous populations.